CA3115020A1 - Antibodies binding to cd3 - Google Patents

Antibodies binding to cd3 Download PDF

Info

Publication number: CA3115020A1
Authority: CA; Canada
Prior art keywords: antibody; domain; seq; antigen binding; fab
Prior art date: 2018-12-21
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

CA3115020A

Other languages

English (en)

French (fr)

Inventor

Anne Freimoser-Grundschober

Thomas Hofer

Ralf Hosse

Ekkehard Moessner

Valeria G. Nicolini

Pablo Umana

Inja Waldhauer

Wolfgang Richter

Alexander KNAUPP

Halina TROCHANOWSKA

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

F Hoffmann La Roche AG

Original Assignee

F Hoffmann La Roche AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2018-12-21

Filing date

2019-12-19

Publication date

2020-06-25

2019-12-19 Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG

2020-06-25 Publication of CA3115020A1 publication Critical patent/CA3115020A1/en

Status Pending legal-status Critical Current

Links

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- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
- C—CHEMISTRY; METALLURGY
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K16/3053—Skin, nerves, brain
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- C—CHEMISTRY; METALLURGY
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- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
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- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C07K2317/565—Complementarity determining region [CDR]
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- C07—ORGANIC CHEMISTRY
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- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
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Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
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Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Cell Biology (AREA)
Neurology (AREA)
Microbiology (AREA)
Oncology (AREA)
Bioinformatics & Cheminformatics (AREA)
Mycology (AREA)
Epidemiology (AREA)
Peptides Or Proteins (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Impression-Transfer Materials And Handling Thereof (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

CA3115020A 2018-12-21 2019-12-19 Antibodies binding to cd3 Pending CA3115020A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP18214994.8		2018-12-21
EP18214994		2018-12-21
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Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20100256340A1 (en)	2009-04-07	2010-10-07	Ulrich Brinkmann	Trivalent, bispecific antibodies
US9676845B2 (en)	2009-06-16	2017-06-13	Hoffmann-La Roche, Inc.	Bispecific antigen binding proteins
WO2016087416A1 (en) *	2014-12-03	2016-06-09	F. Hoffmann-La Roche Ag	Multispecific antibodies
TWI829831B (zh)	2018-12-21	2024-01-21	瑞士商赫孚孟拉羅股份公司	結合cd3之抗體
KR20220028035A (ko) *	2019-07-31	2022-03-08	에프. 호프만-라 로슈 아게	Gprc5d에 결합하는 항체
TWI811703B (zh)	2020-06-19	2023-08-11	瑞士商赫孚孟拉羅股份公司	與ｃｄ３及ｃｄ１９結合之抗體
WO2021255146A1 (en) *	2020-06-19	2021-12-23	F. Hoffmann-La Roche Ag	Antibodies binding to cd3 and cea
CA3176579A1 (en) *	2020-06-19	2021-12-23	F. Hoffmann-La Roche Ag	Antibodies binding to cd3
AU2021291005A1 (en) *	2020-06-19	2023-01-05	F. Hoffmann-La Roche Ag	Antibodies binding to CD3 and FolR1
PE20231552A1 (es) *	2020-06-19	2023-10-03	Hoffmann La Roche	Anticuerpos biespecificos para linfocitos t activados por proteasa
CA3204702A1 (en)	2020-12-17	2022-06-23	F. Hoffmann-La Roche Ag	Anti-hla-g antibodies and use thereof
US20220229062A1 (en) *	2021-01-21	2022-07-21	Diagnostic Biosystems	Method for rapid immunohistochemical detection of an antigen from a biological sample
JP2024512382A (ja)	2021-03-09	2024-03-19	エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト	Ｐｄ－１標的化ｉｌ－２バリアント免疫コンジュゲートと抗ｔｙｒｐ１／抗ｃｄ３二重特異性抗体の併用療法
JP2024523033A (ja)	2021-06-17	2024-06-25	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	新規の三重特異的結合分子
WO2023094569A1 (en)	2021-11-26	2023-06-01	F. Hoffmann-La Roche Ag	Combination therapy of anti-tyrp1/anti-cd3 bispecific antibodies and tyrp1-specific antibodies
AR127887A1 (es)	2021-12-10	2024-03-06	Hoffmann La Roche	Anticuerpos que se unen a cd3 y plap
WO2024027120A1 (en) *	2022-08-05	2024-02-08	Shanghai Kaijin Biotechnology , Ltd	Multi-specific polypeptide complexes
WO2024040127A2 (en) *	2022-08-16	2024-02-22	Northwestern University	Anti-tyrp1 bi-specific t cell engaging protein for treatment of tyrp1-expressing melanoma
WO2024088987A1 (en)	2022-10-26	2024-05-02	F. Hoffmann-La Roche Ag	Combination therapy for the treatment of cancer
WO2024156672A1 (en)	2023-01-25	2024-08-02	F. Hoffmann-La Roche Ag	Antibodies binding to csf1r and cd3
WO2024184287A1 (en)	2023-03-06	2024-09-12	F. Hoffmann-La Roche Ag	Combination therapy of an anti-egfrviii/anti-cd3 antibody and an tumor-targeted 4-1bb agonist

Family Cites Families (106)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US830930A (en)	1905-11-22	1906-09-11	E & T Fairbanks & Co	Weighing-scale.
US4737456A (en)	1985-05-09	1988-04-12	Syntex (U.S.A.) Inc.	Reducing interference in ligand-receptor binding assays
US4676980A (en)	1985-09-23	1987-06-30	The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services	Target specific cross-linked heteroantibodies
US6548640B1 (en)	1986-03-27	2003-04-15	Btg International Limited	Altered antibodies
IL85035A0 (en)	1987-01-08	1988-06-30	Int Genetic Eng	Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
ATE102631T1 (de)	1988-11-11	1994-03-15	Medical Res Council	Klonierung von immunglobulin sequenzen aus den variabelen domaenen.
DE3920358A1 (de)	1989-06-22	1991-01-17	Behringwerke Ag	Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
US5208020A (en)	1989-10-25	1993-05-04	Immunogen Inc.	Cytotoxic agents comprising maytansinoids and their therapeutic use
US5959177A (en)	1989-10-27	1999-09-28	The Scripps Research Institute	Transgenic plants expressing assembled secretory antibodies
US5571894A (en)	1991-02-05	1996-11-05	Ciba-Geigy Corporation	Recombinant antibodies specific for a growth factor receptor
DE122004000008I1 (de)	1991-06-14	2005-06-09	Genentech Inc	Humanisierter Heregulin Antikörper.
GB9114948D0 (en)	1991-07-11	1991-08-28	Pfizer Ltd	Process for preparing sertraline intermediates
US5587458A (en)	1991-10-07	1996-12-24	Aronex Pharmaceuticals, Inc.	Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof
ATE503496T1 (de)	1992-02-06	2011-04-15	Novartis Vaccines & Diagnostic	Biosynthetisches bindeprotein für tumormarker
DE69303494T2 (de)	1992-11-13	1997-01-16	Idec Pharma Corp	Therapeutische verwendung von chimerischen und markierten antikörper gegen menschlichen b lymphozyt beschränkter differenzierung antigen für die behandlung von b-zell-lymphoma
US5731168A (en)	1995-03-01	1998-03-24	Genentech, Inc.	Method for making heteromultimeric polypeptides
GB9603256D0 (en)	1996-02-16	1996-04-17	Wellcome Found	Antibodies
JP4213224B2 (ja)	1997-05-02	2009-01-21	ジェネンテック，インコーポレーテッド	ヘテロマルチマー及び共通成分を有する多重特異性抗体の製造方法
PT994903E (pt)	1997-06-24	2005-10-31	Genentech Inc	Metodos e composicoes para glicoproteinas galactosiladas
US6040498A (en)	1998-08-11	2000-03-21	North Caroline State University	Genetically engineered duckweed
EP1028751B1 (en)	1997-10-31	2008-12-31	Genentech, Inc.	Methods and compositions comprising glycoprotein glycoforms
BR9813365A (pt)	1997-12-05	2004-06-15	Scripps Research Inst	Método para produção e humanização de um anticorpo monoclonal de rato
ES2340112T3 (es)	1998-04-20	2010-05-28	Glycart Biotechnology Ag	Ingenieria de glicosilacion de anticuerpos para la mejora de la citotoxicidad celular dependiente de anticuerpos.
US6737056B1 (en)	1999-01-15	2004-05-18	Genentech, Inc.	Polypeptide variants with altered effector function
WO2001007611A2 (en)	1999-07-26	2001-02-01	Genentech, Inc.	Novel polynucleotides and method for the use thereof
PT1222292E (pt)	1999-10-04	2005-11-30	Medicago Inc	Metodo para regulacao da transcricao de genes exogenos na presenca de azoto
US7125978B1 (en)	1999-10-04	2006-10-24	Medicago Inc.	Promoter for regulating expression of foreign genes
DK2857516T3 (en)	2000-04-11	2017-08-07	Genentech Inc	Multivalent antibodies and uses thereof
NZ603111A (en)	2001-08-03	2014-05-30	Roche Glycart Ag	Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
DE60232265D1 (de)	2001-10-25	2009-06-18	Genentech Inc	Glycoprotein-zusammensetzungen
US20040093621A1 (en)	2001-12-25	2004-05-13	Kyowa Hakko Kogyo Co., Ltd	Antibody composition which specifically binds to CD20
US7749753B2 (en)	2002-04-09	2010-07-06	Kyowa Hakko Kirin Co., Ltd	Cells in which activity of the protein involved in transportation of GDP-fucose is reduced or lost
JPWO2003085107A1 (ja)	2002-04-09	2005-08-11	協和醗酵工業株式会社	ゲノムが改変された細胞
US20050031613A1 (en)	2002-04-09	2005-02-10	Kazuyasu Nakamura	Therapeutic agent for patients having human FcgammaRIIIa
US20040132140A1 (en)	2002-04-09	2004-07-08	Kyowa Hakko Kogyo Co., Ltd.	Production process for antibody composition
US20040259150A1 (en)	2002-04-09	2004-12-23	Kyowa Hakko Kogyo Co., Ltd.	Method of enhancing of binding activity of antibody composition to Fcgamma receptor IIIa
BRPI0316779B8 (pt)	2002-12-16	2023-02-28	Genentech Inc	Anticorpo anti-cd20 humano ou fragmento de ligação ao antígeno do mesmo, seus usos, composição, artigo manufaturado e formulação líquida
NZ591970A (en)	2003-01-22	2012-11-30	Roche Glycart Ag	Fusion constructs and use of same to produce antibodies with increased fc receptor binding affinity and effector function
EP1629012B1 (en)	2003-05-31	2018-11-28	Amgen Research (Munich) GmbH	Pharmaceutical compositions comprising bispecific anti-cd3, anti-cd19 antibody constructs for the treatment of b-cell related disorders
US7235641B2 (en)	2003-12-22	2007-06-26	Micromet Ag	Bispecific antibodies
WO2005097832A2 (en)	2004-03-31	2005-10-20	Genentech, Inc.	Humanized anti-tgf-beta antibodies
CA2561533C (en)	2004-04-13	2015-06-16	Yvo Graus	Anti-p-selectin antibodies
TWI380996B (zh)	2004-09-17	2013-01-01	Hoffmann La Roche	抗ｏｘ４０ｌ抗體
EP1791565B1 (en)	2004-09-23	2016-04-20	Genentech, Inc.	Cysteine engineered antibodies and conjugates
CN101115773B (zh)	2005-02-07	2015-06-10	罗氏格黎卡特股份公司	结合egfr的抗原结合分子,编码它的载体,及其应用
JP5620626B2 (ja)	2005-03-31	2014-11-05	中外製薬株式会社	会合制御によるポリペプチド製造方法
JP5686953B2 (ja)	2005-10-11	2015-03-18	アムゲンリサーチ（ミュンヘン）ゲーエムベーハー	交差種特異的（ｃｒｏｓｓ−ｓｐｅｃｉｅｓ−ｓｐｅｃｉｆｉｃ）抗体を含む組成物および該組成物の使用
PT1999154E (pt)	2006-03-24	2013-01-24	Merck Patent Gmbh	Domínios proteicos heterodiméricos modificados
US20090182127A1 (en)	2006-06-22	2009-07-16	Novo Nordisk A/S	Production of Bispecific Antibodies
US20080044455A1 (en)	2006-08-21	2008-02-21	Chaim Welczer	Tonsillitus Treatment
ES2399075T3 (es)	2006-08-30	2013-03-25	Genentech, Inc.	Anticuerpos multiespecíficos
DE102007001370A1 (de)	2007-01-09	2008-07-10	Curevac Gmbh	RNA-kodierte Antikörper
CN101687915B8 (zh)	2007-04-03	2018-08-03	安进研发（慕尼黑）股份有限公司	跨物种特异性CD3-ε结合结构域
US9266967B2 (en)	2007-12-21	2016-02-23	Hoffmann-La Roche, Inc.	Bivalent, bispecific antibodies
US20090162359A1 (en)	2007-12-21	2009-06-25	Christian Klein	Bivalent, bispecific antibodies
US8242247B2 (en)	2007-12-21	2012-08-14	Hoffmann-La Roche Inc.	Bivalent, bispecific antibodies
MX350962B (es)	2008-01-07	2017-09-27	Amgen Inc	Metodo para fabricar moleculas heterodimericas de fragmentos cristalizables de anticuerpo, utilizando efectos electrostaticos de direccion.
PE20120591A1 (es)	2009-04-02	2012-05-23	Roche Glycart Ag	Anticuerpos multiespecificos que comprenden anticuerpos de longitud completa y fragmentos fab de cadena sencilla
US20100256340A1 (en)	2009-04-07	2010-10-07	Ulrich Brinkmann	Trivalent, bispecific antibodies
CA2759233C (en)	2009-04-27	2019-07-16	Oncomed Pharmaceuticals, Inc.	Method for making heteromultimeric molecules
MX2011011925A (es)	2009-05-27	2011-12-06	Hoffmann La Roche	Anticuerpos triespecificos o tetraespecificos.
US9676845B2 (en)	2009-06-16	2017-06-13	Hoffmann-La Roche, Inc.	Bispecific antigen binding proteins
SG179196A1 (en)	2009-09-16	2012-04-27	Genentech Inc	Coiled coil and/or tether containing protein complexes and uses thereof
SG181952A1 (en)	2009-12-29	2012-07-30	Emergent Product Dev Seattle	Heterodimer binding proteins and uses thereof
JP6022444B2 (ja)	2010-05-14	2016-11-09	ライナットニューロサイエンスコーポレイション	ヘテロ二量体タンパク質ならびにそれを生産および精製するための方法
RU2755066C2 (ru)	2010-06-08	2021-09-13	Дженентек, Инк.	Полученные с помощью генной инженерии антитела с цистеиновыми заменами и их конъюгаты
RS59589B1 (sr)	2010-11-05	2019-12-31	Zymeworks Inc	Dizajniranje stabilnog heterodimernog antitela sa mutacijama u fc domenu
CN105949313B (zh)	2011-03-29	2021-06-15	罗切格利卡特公司	抗体Fc变体
RS57744B1 (sr)	2011-08-23	2018-12-31	Roche Glycart Ag	Bispecifični antigen vezujući molekuli
RU2605390C2 (ru)	2011-08-23	2016-12-20	Рош Гликарт Аг	Биспецифические антитела, специфичные к антигенам, активирующим т-клетки, и опухолевому антигену, и способы их применения
AR087608A1 (es)	2011-08-23	2014-04-03	Roche Glycart Ag	Moleculas biespecificas de union a antigeno activadoras de celulas t
EP2794905B1 (en)	2011-12-20	2020-04-01	MedImmune, LLC	Modified polypeptides for bispecific antibody scaffolds
PL2814587T3 (pl)	2012-02-15	2018-10-31	F.Hoffmann-La Roche Ag	Chromatografia powinowactwa oparta na receptorze Fc
NZ772318A (en)	2012-04-20	2023-06-30	Merus Nv	Methods and means for the production of ig-like molecules
CA2872540A1 (en) *	2012-05-10	2013-11-14	Zymeworks Inc.	Heteromultimer constructs of immunoglobulin heavy chains with mutations in the fc domain
MX2015010350A (es)	2013-02-26	2015-10-29	Roche Glycart Ag	Moleculas de union a antigeno biespecificas que activan la celula t.
PT2961771T (pt) *	2013-02-26	2020-02-28	Roche Glycart Ag	Moléculas de ligação ao antigénio biespecíficas para ativação das células t, específicas para cd3 e cea
CN105555804B (zh) *	2013-08-07	2020-12-25	阿菲姆德股份有限公司	对EGFRvIII有特异性的抗体结合位点
KR20230155605A (ko)	2013-12-20	2023-11-10	제넨테크, 인크.	이중 특이적 항체
UA117289C2 (uk)	2014-04-02	2018-07-10	Ф. Хоффманн-Ля Рош Аг	Мультиспецифічне антитіло
EP3174897B1 (en)	2014-07-29	2020-02-12	F.Hoffmann-La Roche Ag	Multispecific antibodies
BR112017001818A2 (pt) *	2014-07-29	2017-11-21	Pfizer	receptores antigênicos quiméricos específicos para egfrviii para imunoterapia de câncer
WO2016016859A1 (en) *	2014-07-31	2016-02-04	Amgen Research (Munich) Gmbh	Optimized cross-species specific bispecific single chain antibody constructs
CN106661120B (zh)	2014-08-04	2021-10-01	豪夫迈·罗氏有限公司	双特异性t细胞活化性抗原结合分子
KR20170052600A (ko)	2014-09-12	2017-05-12	제넨테크, 인크.	시스테인 가공된 항체 및 콘주게이트
LT3789402T (lt) *	2014-11-20	2022-09-26	F. Hoffmann-La Roche Ag	Kompleksinė terapija, naudojant t ląsteles aktyvinančias bispecifines antigeną surišančias molekules ir pd-1 ašį surišančius antagonistus
PT3221356T (pt)	2014-11-20	2020-10-29	Hoffmann La Roche	Moléculas de ligação ao antigénio biespecíficas ativadoras das células t contra folr1 e cd3
AU2016252773B2 (en)	2015-04-24	2022-06-02	Genentech, Inc.	Multispecific antigen-binding proteins
TWI744242B (zh) *	2015-07-31	2021-11-01	德商安美基研究（慕尼黑）公司	Egfrviii及cd3抗體構築體
WO2017055393A1 (en) *	2015-10-02	2017-04-06	F. Hoffmann-La Roche Ag	Anti-cd3xtim-3 bispecific t cell activating antigen binding molecules
AR106365A1 (es) *	2015-10-02	2018-01-10	Hoffmann La Roche	Moléculas biespecíficas de unión a antígeno activadoras de células t
EP3356410B1 (en) *	2015-10-02	2021-10-20	F. Hoffmann-La Roche AG	Bispecific anti-ceaxcd3 t cell activating antigen binding molecules
CN107949574A (zh) *	2015-10-02	2018-04-20	豪夫迈·罗氏有限公司	双特异性t细胞活化性抗原结合分子
WO2017055318A1 (en) *	2015-10-02	2017-04-06	F. Hoffmann-La Roche Ag	Cd33xcd3 bispecific t cell activating antigen binding molecules
CN114891102A (zh)	2015-10-29	2022-08-12	豪夫迈·罗氏有限公司	抗变体Fc区抗体及使用方法
CA2954014A1 (en) *	2016-01-21	2017-07-21	Oi Kwan WONG	Chimeric antigen receptors targeting epidermal growth factor receptor variant iii
JP7022123B2 (ja) *	2016-09-30	2022-02-17	エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト	Ｃｄ３に対する二重特異性抗体
WO2018223004A1 (en) *	2017-06-01	2018-12-06	Xencor, Inc.	Bispecific antibodies that bind cd20 and cd3
TWI829831B (zh)	2018-12-21	2024-01-21	瑞士商赫孚孟拉羅股份公司	結合cd3之抗體
WO2020127618A1 (en)	2018-12-21	2020-06-25	F. Hoffmann-La Roche Ag	Tumor-targeted agonistic cd28 antigen binding molecules
KR20220028035A (ko)	2019-07-31	2022-03-08	에프. 호프만-라 로슈 아게	Gprc5d에 결합하는 항체
AU2021291405A1 (en)	2020-06-19	2022-09-29	F. Hoffmann-La Roche Ag	Immune activating Fc domain binding molecules
WO2021255146A1 (en)	2020-06-19	2021-12-23	F. Hoffmann-La Roche Ag	Antibodies binding to cd3 and cea
AU2021291005A1 (en)	2020-06-19	2023-01-05	F. Hoffmann-La Roche Ag	Antibodies binding to CD3 and FolR1
TWI811703B (zh)	2020-06-19	2023-08-11	瑞士商赫孚孟拉羅股份公司	與ｃｄ３及ｃｄ１９結合之抗體
CA3204702A1 (en)	2020-12-17	2022-06-23	F. Hoffmann-La Roche Ag	Anti-hla-g antibodies and use thereof

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US11591397B2 (en)	2023-02-28
CO2021008568A2 (es)	2021-07-30
JP7061733B2 (ja)	2022-04-28
MY194642A (en)	2022-12-09
CL2021001506A1 (es)	2021-12-24
TW202428614A (zh)	2024-07-16
TW202212361A (zh)	2022-04-01
AU2022206732A1 (en)	2022-09-29
KR20240155361A (ko)	2024-10-28
TW202039566A (zh)	2020-11-01
EP3897847A1 (en)	2021-10-27
KR102720337B1 (ko)	2024-10-24
CN113195056A (zh)	2021-07-30
CN113621062A (zh)	2021-11-09
JP2022513493A (ja)	2022-02-08
BR112021011939A2 (pt)	2021-09-14
CN113621062B (zh)	2024-07-02
AR117727A1 (es)	2021-08-25
CO2021011065A2 (es)	2021-09-09
TWI818387B (zh)	2023-10-11
IL283939A (en)	2021-07-29
PE20211603A1 (es)	2021-08-18
WO2020127619A1 (en)	2020-06-25
AU2019410075A1 (en)	2021-04-15
CR20210325A (es)	2021-07-20
SG10202105790QA (en)	2021-07-29
KR20210094588A (ko)	2021-07-29
US20200270347A1 (en)	2020-08-27
SG10202105788SA (en)	2021-06-29
SG11202102859TA (en)	2021-04-29
CN118271445A (zh)	2024-07-02
AU2019410075B2 (en)	2022-08-25
US20210403562A1 (en)	2021-12-30
CL2021003132A1 (es)	2022-08-19
TWI829831B (zh)	2024-01-21
US20240042022A1 (en)	2024-02-08
CR20210330A (es)	2021-07-20
MA54514A (fr)	2022-03-30
US20230277662A1 (en)	2023-09-07
US11672858B2 (en)	2023-06-13
MX2021007307A (es)	2021-07-07
CN113195056B (zh)	2024-05-07

Publication	Publication Date	Title
US11591397B2 (en)	2023-02-28	Bispecific antibody molecules binding to CD3 and EGFRvIII
US11827711B2 (en)	2023-11-28	Antibodies binding to NKG2D
US20220010015A1 (en)	2022-01-13	Antibodies binding to cd3
US20230416411A1 (en)	2023-12-28	Antibodies binding to cd3 and folr1
US11780920B2 (en)	2023-10-10	Antibodies binding to CD3 and CD19
CA3161390A1 (en)	2021-06-24	Antibodies binding to hla-a2/mage-a4
WO2021255146A1 (en)	2021-12-23	Antibodies binding to cd3 and cea
US20240018240A1 (en)	2024-01-18	Antibodies binding to cd3 and plap
RU2810924C2 (ru)	2024-01-09	Антитела, связывающиеся с cd3

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